DESVENLAFAXINE WITHDRAWAL AND TAPERING HELP

Desvenlafaxine (Pristiq) was approved by the FDA in 2007 (for Wyeth Laboratories) and is the active metabolite of Venlafaxine (Effexor), which lost its patent protection the same year. Desvenlafaxine was approved in Canada and the United States. Desvenlafaxine has higher rates of withdrawal symptoms (discontinuation syndrome) than other SNRI or SSRI antidepressants. For some patients the symptoms can be severe and are considered intolerable. A gradual taper is recommended to minimize symptoms. Desvenlafaxine is the active metabolite of Venlafaxine and can have significant withdrawal symptoms.

Desvenlafaxine was approved by the FDA in 2007 (for Wyeth Laboratories) and is the active metabolite of Venlafaxine (Effexor), which lost its patent protection the same year. Desvenlafaxine was approved in Canada and the United States, but the European Union declined stating in part, "they had some concerns and was of the provisional opinion that Desvenlafaxine could not have been approved for the treatment of major depressive disorder [and] overall, the effectiveness of Desvenlafaxine had not been shown convincingly. In relation to its parent substance, Venlafaxine, Desvenlafaxine seemed to be less effective with no advantages in terms of safety and tolerability." Wyeth withdrew its application for approval in the European Union.

December 2015 Pfizer announced the results from a Phase 3 study evaluating the efficacy, safety and tolerability of Pristiq (sustained release) in pediatric patients ages 7-17 with Major Depressive Disorder. The results indicate that Pristiq (Desvenlafaxine) were not significantly different from placebo. 

Desvenlafaxine has higher rates of withdrawal symptoms (discontinuation syndrome) than other SNRI or SSRI antidepressants. For some patients the symptoms can be severe and are considered intolerable. A gradual taper is recommended to minimize symptoms.

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DESVENLAFAXINE WITHDRAWAL SYMPTOMS MAY INCLUDE:

aggression, anxiety, balance issues , blurred vision, brain zaps, concentration impairment, constipation, crying spells, depersonalization, diarrhea, dizziness. electric shock sensations, fatigue, flatulence, flu-like symptoms, hallucinations, hostility, highly emotional, indigestion, irritability, impaired speech, insomnia, jumpy nerves, lack of coordination, lethargy, migraine headaches / increased headaches, nausea, nervousness, over-reacting to situations, paranoia, repetitive thoughts or songs, sensory & sleep disturbances, severe internal restlessness (akathisia), stomach cramps, tremors, tinnitus (ear ringing or buzzing), tingling sensations, troubling thoughts, visual hallucinations / illusions, vivid dreams, speech or visual changes, worsened depression 

DESVENLAFAXINE SIDE EFFECTS MAY INCLUDE: 

allergic reaction (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives), irregular heartbeat or pulse, low blood pressure (dizziness, weakness), high blood pressure (severe headache, blurred vision), chills or fever, unusual bleeding or bruising, rash or hives, Suicidal Ideation, Headache, tremor, nervousness, or anxiety; difficulty concentrating, constipation, nausea, diarrhea, dry mouth, or changes in appetite or weight, weakness, increased sweating, sleeping or insomnia, decreased sex drive, impotence, or difficulty having an orgasm

DESVENLAFAXINE ADVERSE REACTIONS MAY INCLUDE: per PDR 

Severe: seizures,  angioedema,  pancreatitis,  suicidal ideation,  SIADH,  GI bleeding,  cardiomyopathy,  myocardial infarction,  Stevens-Johnson syndrome,  toxic epidermal necrolysis,  erythema multiforme,  eosinophilic pneumonia,  serotonin syndrome,  neonatal abstinence syndrome

Moderate: withdrawal, constipation, impotence, hypercholesterolemia, orthostatic hypotension, proteinuria, ejaculation dysfunction, hypertriglyceridemia, blurred vision, hypertension, dystonic reaction, teeth grinding (bruxism), sinus tachycardia, urinary retention, hyperprolactinemia, elevated hepatic enzymes, peripheral vasodilation, mania, hallucinations, depression, akathisia, impulse control symptoms, hostility, hyponatremia, platelet dysfunction, hematoma, bleeding, dyspnea

Mild: nausea, xerostomia,   hyperhidrosis,   dizziness,  insomnia,   drowsiness,   fatigue,   anore,   anxiety,   abnormal dreams,   yawning,   chills,   weight gain,   dysgeusia,   syncope,   photosensitivity,   rash, a lopecia, tinnitus,   flushing,   musculoskeletal pain,   asthenia,   weight loss, i rritability,   restlessness,   ecchymosis,  p etechiae,   cough

DESVENLAFAXINE BOXED WARNINGS: per PDR  

Children,  suicidal ideation

Desvenlafaxine is not FDA approved for the treatment of major depressive disorder (MDD) in children or adolescents. Efficacy in MDD was not demonstrated in two 8-week controlled trials of 587 pediatric patients 7 to 17 years of age. In addition, more patients receiving desvenlafaxine than placebo had a decrease in body weight of 3.5% or greater from their baseline weight (14% to 22% vs. 7%). During long-term extension studies in the same population, the mean changes in weight approximated expected changes based on data from age and gender-matched controls. In October 2004, the FDA directed manufacturers of all antidepressants to add a boxed warning to their product labels detailing the risk of suicide in pediatric patients. The risk of suicidality for these drugs was identified in a pooled analysis of 24 placebo-controlled trials (n = 4,400) lasting up to 16 weeks in pediatric patients with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders. The analysis showed a greater risk of suicidality during the first few months of treatment in those receiving antidepressants. The average risk of such events on drug was 4% and 2% for placebo; however, no suicides occurred in these trials. Pooled analysis of short-term clinical trials during early phase treatment with antidepressants in young adults (18 to 24 years) also showed an increased risk of suicidal thinking and behavior. The clinical need for an antidepressant in pediatrics or young adults for any use must be weighed against the risk of increased suicidality; patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior, particularly within the first few months of starting therapy or during dose changes. It is unknown if the suicidality risk in children or young adults extends to longer-term therapy. The possibility of a suicide attempt is inherent in patients with depressive symptoms, whether these occur in primary depression or in association with another primary disorder. All patients with a history of suicidal ideation or behaviors and those with a prominence of suicidal ideation prior to treatment should be closely monitored during treatment with desvenlafaxine. In patients who exhibit worsening of depression or suicidality, a decision should be made to change or discontinue treatment. If discontinuing, the medication should be tapered as rapidly as possible, but with recognition that abrupt discontinuation can also cause adverse symptoms. All antidepressants should be prescribed in the smallest quantity consistent with good patient management to reduce the risk of overdose.

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According to the FDA:

Clinical Worsening/Suicide Risk: Monitor for clinical worsening and suicide risk 

Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions: Serotonin syndrome or NMS-like reactions have been reported with SSRIs and SNRIs. Discontinue Pristiq and initiate supportive treatment.

Elevated Blood Pressure: Has occurred with PRISTIQ. Hypertension should be controlled before initiating treatment. Monitor blood pressure regularly during treatment 

Abnormal Bleeding: PRISTIQ may increase the risk of bleeding events. Patients should be cautioned about the risk of bleeding associated with the concomitant use of PRISTIQ and NSAIDs, aspirin, or other drugs that affect coagulation 

Narrow-angle Glaucoma: Mydriasis has occurred with PRISTIQ. Patients with raised intraocular pressure or those at risk of angle-closure glaucoma should be monitored 

Activation of Mania/Hypomania: Has occurred. Use cautiously in patients with Bipolar Disorder. Caution patients about the risk of activation of mania/hypomania 

Cardiovascular/Cerebrovascular Disease: Use cautiously in patients with cardiovascular or cerebrovascular disease

Cholesterol and Triglyceride Elevation: Have occurred. Use cautiously in patients with lipid metabolism disorders. Consider monitoring serum cholesterol and triglyceride

Discontinuation Symptoms: Have occurred. Taper the dose when possible and monitor for discontinuation symptoms 

Renal Impairment: Reduces the clearance of PRISTIQ. Dosage adjustment is necessary in severe and ESRD. In moderate renal impairment, the dose should not exceed 50 mg/day 

Seizure: Can occur. Use cautiously in patients with seizure disorder 

Hyponatremia: Can occur in association with SIADH

Drugs Containing Desvenlafaxine or Venlafaxine: Should not be used concomitantly with PRISTIQ (5.13). Interstitial Lung Disease and Eosinophilic Pneumonia: Can occur

REFERENCES:

https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021992s030lbl.pdf

https://www.nami.org/Learn-More/Treatment/Mental-Health-Medications/Types-of-Medication/Desvenlafaxine-(Pristiq)

https://www.karger.com/Article/Pdf/491524

https://www.tandfonline.com/doi/abs/10.1185/03007995.2015.1020365

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